Bjørn Richelsen

• Professor
• Professor at Aarhus University Hospital

Objectives We examined the association between Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) and fracture risk, including major osteoporotic fractures (MOF), and the use of anti-osteoporosis medication (AOM). While RYGB is associated with impaired bone health and increased fracture risk, it remains uncertain whether SG has a similar im...

Objective This study investigates the overall and cause‐specific mortality in males and females with anorexia nervosa (AN) from 1977 to 2018, focusing on the impact of psychiatric comorbidity on mortality risk, a less explored aspect despite a high prevalence in patients with AN. Method We conducted a nationwide population‐based cohort study in De...

Purpose After Roux-en-Y gastric bypass (RYGB), few patients develop severe complications, which ultimately may require reversal of RYGB. We aimed to examine the effect of reversal of RYGB on symptoms and well-being. Materials and Methods Via contact to medical and surgical departments treating patients with RYGB, we identified 18 patients, who had...

Objective: To examine the association between hospital-diagnosed overweight/obesity and incident cardiovascular disease (CVD) according to the time period of the overweight/obesity diagnosis. Design: Cohort study. Methods: From Danish national health registries, we identified all residents with a first-time hospital-based overweight/obesity diagnos...

Prior research has reported increased fracture risk in patients with anorexia nervosa (AN), but more knowledge on the long‐term risk, and the effect of age, male sex and time related changes is still needed. We examined the long‐term (up to 40 years) fracture risk among patients with AN compared to a matched comparison cohort from the general popul...

Purpose Obesity may alter the severity of infection with Coronavirus disease 2019 (COVID‐19). Age may impact the association between body weight and severity of COVID‐19 in patients with obesity. The aim of the study was to examine the association between obesity and severity of infection in a Danish cohort hospitalized with COVID‐19 in the initial...

Aim: Bariatric surgery improves insulin sensitivity and glucose tolerance in obese individuals with type 2 diabetes (T2D), but there is a lack of data comparing the underlying metabolic mechanisms after the 2 most common surgical procedures Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG). This study was designed to assess and c...

Background High carbohydrate, i.e., sugars, intake potentially drives the liver into a lipogenic state leading to elevated plasma fatty acids. Excessive intake of saturated fat and sugar-sweetened soda induces liver fat accumulation, but studying the effect of high intake from sugar-sweetened soda on the de novo lipogenesis (DNL) fatty acids in lon...

Insulin resistance in skeletal muscle in type 2 diabetes (T2D) is characterized by more pronounced metabolic and molecular defects than in obesity per se. There is increasing evidence that adipose tissue dysfunction contributes to obesity-induced insulin resistance in skeletal muscle. Here, we used an unbiased approach to examine if adipose tissue...

The early effects of bariatric surgery on insulin secretion and action in obese subjects with type 2 diabetes (T2D) remains poorly investigated. Here we assessed the mechanisms resulting in improved glucose intolerance using the oral minimal model approach. An oral glucose tolerance test was performed before and 2 months after bariatric surgery in...

Purpose Data on long-term mortality among patients with hospital-diagnosed overweight/obesity are limited. Thus, we aim to examine 40-year mortality among patients with hospital-diagnosed overweight/obesity, including cause-specific deaths, secular time trends, and potential effect modification by age, comorbidity, and socioeconomic factors. Patie...

The ongoing coronavirus disease 2019 (COVID‐19) pandemic calls for identification of risk factors, which may help to identify people at enhanced risk for severe disease outcomes to improve treatment and, if possible, establish prophylactic measures. This study aimed to determine whether individuals with obesity compared to individuals with normal w...

Background/objectives Bariatric surgery as treatment of obesity is increasing worldwide. No guidelines exist on which type of bariatric procedure to choose for the individual patient. This study aims to compare Roux-en-Y Gastric bypass (RYGB) and sleeve gastrectomy (SG) with respect to weight loss, complications, comorbidities, and quality of life...

Objective: To examine the association between body mass index (BMI) and mortality after hospitalization for infection because obesity is associated with increased energy reserves that may protect against death from severe infections. Patients and methods: Of 76,044 patients admitted with a primary infection diagnosis from January 1, 2011, to Sep...

Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as “browning”, serves as an alt...

Brown adipose tissue (BAT) has gained growing interest as a potential target for treatment of obesity. Currently, the most widely used technique/method for in vivo measurements of BAT activity in humans is ¹⁸FDG PET/CT. To supplement these investigations novel radiation-free methods are warranted. Deuterium metabolic imaging (DMI) is a novel modali...

Background Postprandial hypoglycemia is a relatively common complication after Roux-en-Y gastric bypass (RYGB). The etiology remains incompletely understood and the association between biochemical hypoglycemia and hypoglycemic symptoms is unclear. Objectives To evaluate the association between postprandial hormonal responses and biochemical and sy...

Growth hormone (GH) exerts IGF-I dependent protein anabolic and direct lipolytic effects. Obesity reversibly suppresses GH secretion driven by elevated FFA levels, whereas serum IGF-I levels remain normal or elevated due to elevated portal insulin levels. Fasting in lean individuals suppresses hepatic IGF-I production and increases pituitary GH rel...

Hypoglycemia is common in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) and constitutes a major limiting factor in achieving glycemic control among people with diabetes. While hypoglycemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glyce...

Background: Obesity is associated with metabolic abnormalities that predispose patients to increased cancer risk. Contemporary data on the long-term risk of specific cancers are sparse among patients with hospital-diagnosed overweight and obesity. Objectives: To examine the overall cancer incidence and specific site-related cancer incidences amo...

Since publication the authors noticed an error in Tables 2, 3, and 4 of the original article, where the pre-intervention values were presented by mean and SD instead of mean and SE as described in the table text. The correct tables are reproduced below where SD’s are replaced by SE’s.

Purpose Brown adipose tissue (BAT) activation in humans has gained interest as a potential target for treatment of obesity and insulin resistance. In rodents, BAT is primarily induced through beta-3-adrenergic receptor (ADRB3) stimulation, whereas the primary beta-adrenergic receptors (ADRBs) involved in human BAT activation are debated. We evaluat...

Circulating BDNF is higher in women than in men and suggested to be affected by changes in food intake, body weight, and exercise. The purpose of this study was to compare BDNF concentrations in women and men during a 12-week weight loss intervention. Using a previously published 12-week randomized study, serum BDNF was assessed at baseline and aft...

Purpose Health care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals. Patients and methods We linked data from the Danish Nation...

Background Roux-en-Y gastric bypass (RYGB) has been associated with negative effects on bone. Whether this association is affected by pre-surgical type 2 diabetes (T2D) and surgically induced diabetes remission is unknown. Methods In this cross-sectional, matched cohort study 6 years after RYGB, we investigated bone health in 96 individuals with b...

Aims/hypothesis The aim of this study was to examine the effect of Roux-en-Y gastric bypass (RYGB) surgery on diabetes remission, subsequent diabetes relapse and micro- and macrovascular complications in individuals with type 2 diabetes and obesity (BMI >35 kg/m²) in a real-world setting. Methods This was a population-based cohort study of 1111 in...

The capacity to increase energy expenditure makes brown adipose tissue (BAT) a putative target for treatment of metabolic diseases such as obesity. Presently, investigation of BAT in vivo is mainly performed by fluoro-d-glucose positron emission tomography (FDG PET)/CT. However, non-radioactive methods that add information on, for example, substrat...

Objective Following Roux‐en‐Y gastric bypass (RYGB), elevated parathyroid hormone (PTH) levels potentially harmful to bone health are commonly observed. Owing to assumed superior absorption, calcium citrate is often recommended over calcium carbonate following RYGB for the treatment of elevated PTH. We aimed to investigate the impact of either calc...

Metformin is the most widely prescribed oral antidiabetic drug worldwide. Despite well‐documented beneficial effects on health outcomes in diabetic patients, the target organs that mediate the effects of metformin remain to be established. In adult humans, brown adipose tissue (BAT) can influence basic metabolic rate, making BAT an attractive targe...

Postprandial hypoglycaemia with endogenous hyper-insulinaemia is relatively common after gastric bypass (GB) surgery. However, alternative aetiologies of hypoglycaemia should be kept in mind. We report a case of severe hypo-glycaemia in a patient who had previously undergone GB surgery for morbid obesity. Hypoglycaemic episodes differed from typica...

Background Data are sparse on the range of BMI among patients acutely admitted to general hospitals. We investigated BMI values and associated patient characteristics, reasons for hospital admission, and mortality in Denmark. Methods We identified all persons with an acute inpatient admission 2011–2014 in Central Denmark Region and assessed BMI me...

Anatomical Therapeutic Chemical Classification System codes (ATC-codes) for prescription medications from the Danish National Prescription Health Service Database. (DOCX)

Prevalences of prehospital medication users in the cohort according to BMI category. (DOCX)

The 15 most common ICD-10 diagnoses at the three-digit level in the Danish National Patient Registry, according to body mass index category. (DOCX)

ICD-10 codes for conditions included in the Charlson Comorbidity Index. (DOCX)

Prevalence of comorbidities in the Charlson Comorbidity Score, by BMI category. (DOCX)

Diagnosis codes for selected diseases and according to ICD-10 chapters used for disease categories. (DOCX)

Background/objectives: Milk contributes with saturated fat, but randomized controlled trials (RCT) on the effects of dairy on the risk of type 2 diabetes (T2D) where dairy is given as whole foods are scarce. The objective of our study was to investigate the long-term effects of semi-skimmed milk on insulin sensitivity and further to compare milk w...

The authors have discovered a coding error in the statistical analysis syntax file used for the mixed-effect model analyses in this paper. The error has led to differences (first decimal) in the estimates for the main results.

Background & aims Bariatric surgery increases the risk of micronutrient deficiencies, including vitamin B12 (B12) deficiency. We analysed early changes in biomarkers of B12 status following bariatric surgery. Methods We prospectively included adult patients (n = 27) referred for either Roux-en-Y Gastric Bypass (RYGB) (n = 19) or Sleeve Gastrectomy...

Brown adipose tissue with its constituent brown adipocytes is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. The molecular control of brown adipocyte differentiation and function has been extensively studied in mice, but relatively little...

Micrographs of TERT-hWA and TERT-hBA pre-adipocytes and adipocytes. Representative micrographs of Oil red O-stained TERT-hBA and TERT-hWA cells at day 0 and 12 at passage 7–9. (TIF)

Expression of brown and brown-like adipocyte type-selective marker genes. (A) Relative mRNA levels of the proposed brown and brown-like adipocyte-selective genes ZIC1, LHX8, TMEM26 and CD137 in hBAT and hWAT. Expression levels were normalized to TBP levels. The normalized expression in hWAT was set to 1, except for TMEM26 in which hBAT was set to 1...

Primers used for RT-qPCR. (PDF)

Ingenuity Pathway Analysis ‘Disease and Biology’ data used to generate the heat map shown in Figure 3G.DOI: http://dx.doi.org/10.7554/eLife.23813.017

Ingenuity Pathway Analysis results for P3.DOI: http://dx.doi.org/10.7554/eLife.23813.015

Differential expression analysis data.DOI: http://dx.doi.org/10.7554/eLife.23813.012

Ingenuity Pathway Analysis results for P1.DOI: http://dx.doi.org/10.7554/eLife.23813.013

Ingenuity Pathway Analysis results for P2.DOI: http://dx.doi.org/10.7554/eLife.23813.014

Data used to generate the heat maps shown in Figure 3C.DOI: http://dx.doi.org/10.7554/eLife.23813.016

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massi...

Brown adipose tissue thermogenesis at the cost of energy is not only important for the development of obesity, but also possesses great promise in anti-obesity treatment. Uncoupling protein 1 (UCP1) expression has been reported to be under control of the intracellular deacetylase SIRT1. Here, we investigated the effect and mechanism of inflammation...

Background: Fibroblast growth factor 21 (FGF21) is elevated in obesity. Objectives: We investigated the circulating level of FGF21 and the expression of FGF21, beta-klotho (KLB), and FGF receptor 1 (FGFR1) in adipose tissue in relation to weight, fat distribution, and Roux-en-Y gastric bypass (RYGB)-induced weight loss. Setting: The Department...

Abstract Context: Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications. Objective: To investigate effects of long-term RSV treatment on inflammation and MetS. Setting an...

Objective: This investigation was conducted to determine whether dietary supplementation with a specific leucine-rich whey protein compound improves physical function and muscle strength in osteopenic elderly people compared to soy protein and placebo. Design, participants and setting: The study was a 16-week randomized single blinded placebo contr...

Objective: To examine rates of acute inpatient hospital admissions patients undergoing Roux-en-Y gastric bypass (RYGB) surgery and a matched population-based comparison cohort. Summary background data: Little is known about the admission rates before and after RYGB. Methods: Nationwide population-based cohort study, including all 9985 patients...

Brown adipose tissue (BAT) is activated by extracellular norepinephrine (NE) released by the sympathetic nervous system. The extracellular concentration of NE is additionally regulated by the disappearance/degradation of NE. Recent studies have introduced the organic cation transporter 3 (OCT3) as a possible contributor in the regulation of NE in a...

Aim/hypothesis: Our aim was to investigate the association between the macrophage-activation marker soluble CD163 (sCD163), adiponectin, C-reactive protein (CRP) and changes in glycaemia, insulin resistance and insulin secretion in individuals at high risk of type 2 diabetes mellitus. Methods: This prospective study included 1014 individuals at...

A wide range of complications may occur after Roux-en-Y gastric bypass (RYGB) surgery, including surgical, medical/nutritional, and psychiatric complications. Some of the nutritional complications such as anaemia, dumping and hypoglycaemia may present rather unspecific symptoms that may easily not be diagnosed as complications after RYGB. Focus on...

Background: Few population-based studies provide data on mortality after bariatric surgery. We hypothesized that hypoglycemia could be an underdiagnosed cause of death. Objectives: To examine perioperative, all-cause, and cause-specific long-term mortality in Roux-en-Y gastric bypass (RYGB) patients versus population comparisons. Setting: Dani...

Background: Roux-en-Y gastric bypass (RYGB) alters glucose metabolism and can cause postprandial hypoglycemia. Continuous glucose monitoring (CGM) has been proposed as an evaluation tool in hypoglycemic RYGB individuals. The objective of this study is to investigate the use of CGM in clinical decision-making including diagnosing hypoglycemia and e...

Adipose tissue inflammation is believed to play a pivotal role in the development obesity-related morbidities such as insulin resistance. However, it is not known how this (low-grade) inflammatory state develops. It has been proposed that the leakage of lipopolysaccharides (LPS), originating from the gut microbiota, through the gut epithelium could...

Total list of identified proteins by SILAC-MS method and the individual ratios of biological replicates. (XLSX)

Total list of proteins either up- or downregulated by LPS. (XLSX)

List of primer pairs used. (DOCX)

Background: Protein-rich beverages are widely used clinically to preserve muscle protein and improve physical performance. Beverages with high contents of leucine or its keto-metabolite β-hydroxy-β-methylbutyrate (HMB) are especially anabolic in muscle, but it is uncertain whether this also applies to catabolic conditions such as fasting and wheth...

Objectives: To evaluate changes over time in drug use among patients undergoing Roux-en-Y gastric bypass (RYGB) surgery and a matched population-based comparison cohort. Background: A little is known about the prescription drug use before and after RYGB surgery. Methods: Nationwide population-based cohort study included 9908 patients undergoing RYG...

Background: Roux-en-Y gastric bypass (RYGB) results in pronounced weight loss in morbidly obese patients but may also cause adverse effects like early dumping and hypoglycemia. Prevalence data on these complications and their potential predictors are sparse. Objective: To assess the prevalence and possible predictors of early dumping and hypogly...

In conclusion: Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulatio...

Primary and secondary antibodies used for Western blot analysis. (DOCX)

Western blot analysis on skeletal muscle. AKT (isoform 2), AS160, glycogen synthase, cytochrome c, pyruvate dehydrogenase, SDHA and HSP60 were investigated by Western blot analysis. However, no significant alterations in protein expression were induced by resveratrol and/or LPS. Data are presented as means ± SEM. (TIF)

Importance Population-based studies on the prevalence of symptoms after Roux-en-Y gastric bypass (RYGB) surgery are sparse. Knowledge about possible predictors of these symptoms is important for prevention.Objectives To examine patients’ overall well-being and the prevalence and predictors of medical, nutritional, and surgical symptoms after RYGB...

The central melanocortin system is broadly involved in the regulation of mammalian nutrient utilization. However, the function of melanocortin receptors (MCRs) expressed directly in peripheral metabolic tissues is still unclear. The objective of this study was to investigate the lipolytic capacity of MC1-5R in differentiated adipocytes versus intac...

Obese subjects are often characterized by low plasma 25-hydroxy-vitamin D (25OHD) levels. Many explanations for this association have been proposed. Low plasma 25OHD is associated with obesity-related comorbidities such as insulin resistance, type 2 diabetes mellitus, and low-grade inflammation. In this review, we discuss the proposed mechanisms fo...

Sucrose-sweetened soft drinks (SSSDs) are associated with the development of metabolic disorders. Fructose is a major component of SSSDs and is demonstrated to induce uric acid (UA) production and stimulate fat accumulation independent of excess caloric intake. UA induce insulin resistance and low-grade inflammation, suggesting that UA may have a c...

Background: Resveratrol is a naturally occurring polyphenol with purported inhibitory effects on prostate growth and cancer development. A number of studies have demonstrated that resveratrol reduces prostate growth in animal models and reduces prostate cell growth in vitro. Based on these pre-clinical findings, interest in resveratrol is increasi...

Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism. Eight young, healthy, lean males were investigated three times in randomized order: (i) normal c...

Previous research suggests that patients using glucocorticoids may be at increased risk of postoperative bleeding and infection after major surgery. The objective was to investigate the association between preoperative glucocorticoid use and risk of bleeding and infection after Roux-en-Y gastric bypass surgery (RYGB). Nationwide cohort study of 13,...

Objective Soluble CD163 (sCD163) is a new marker of obesity-related metabolic complications. sCD163 and CD163 mRNA were investigated in relation to the fat distribution at baseline and 12 months after Roux-en-Y gastric bypass (RYGB).Methods Thirty-one obese subjects (BMI: 42.3 ± 4.7 kg/m2) were enrolled. Subcutaneous (SAT) and visceral adipose tiss...

CD163-positive macrophages are highly expressed in the human adipose tissue (AT) particularly from obese individuals. Little is, however, known about the regulation of CD163 mRNA and the protein level of sCD163 in human AT. We aimed to examine the regulation of CD163 and sCD163 in AT. Human subcutaneous AT samples (n=5) were stimulated with dexamet...

The literature reports a large variety of adverse reactions to potassium iodide. A severe hypersensitivity reaction to potassium iodide in a 51-year-old woman with Graves' thyrotoxicosis is described. Following administration the patient developed sialadenitis, conjunctivitis, stomatitis and acneiform iododerma that responded dramatically to withdr...

Treatment of severe obesity by Roux-en-Y gastric bypass (RYGB) causes sustained weight losses and improves health complica-tions. RYGB is, however, also associated with adverse effects. Dumping is a well-known complication causing invalidating symptoms, and lately there have been mounting concerns about post-RYGB hypoglycaemia. This condition is ch...

Treatment of severe obesity with Roux-en-Y gastric bypass (RYGB) results in pronounced weight loss but also in various nutritional complications. Iron deficiency anaemia is one of the most common nutritional complications due to reduced uptake of iron after this operation. Premenopausal women are particularly at risk of developing iron deficiency a...

Context: Central obesity in polycystic ovary syndrome (PCOS) is associated with increased inflammatory markers and increased risk for type 2 diabetes. Objective: To evaluate if improved body composition during treatment with metformin (M) vs. oral contraceptive pills (OCP) was associated with changes in circulating adiponectin, interleukin (IL)-...

In addition to permanent weight loss various complications are associated with bariatric surgery. This case report describes two women who developed pronounced anaemia after Roux-en-Y gastric bypass (RYGB), which had to be treated with intravenous iron substitution. Anaemia due to reduced iron uptake is common after RYGB and menstruating women are...

In parallel with the increasing incidence of obesity there has been an increase in the number of bariatric surgery procedures performed, and as a consequence we have seen an increasing prevalence of medical and nutritional complications in recent years. Some of the important complications are dumping syndrome and reactive hypoglycaemia, and these c...

Background: High levels of free fatty acids (FFA) have been suggested to be one of the underlying mechanisms for adipose tissue (AT) inflammation and dysfunction in obesity. Human AT produces several adipokines including monocyte chemoattractant protein-1 (MCP-1), which are involved in the pathogenesis of obesity-mediated inflammation. Objective:...

Objective: Adipose tissue (AT) macrophages are increased in obesity and associated with low grade inflammation. We aimed to characterize the phenotype of AT macrophages in humans in relation to obesity and insulin resistance. Design: Gene-expression levels of general macrophage markers (CD68 and CD14), proinflammatory markers/M1 (TNF-α, MCP-1, a...